Effects of BM-573, a thromboxane A2 modulator on systemic hemodynamics perturbations induced by U-46619 in the pig. 2005

Vincent Tchana-Sato, and Jean-Michel Dogné, and Bernard Lambermont, and Alexandre Ghuysen, and David Magis, and Philippe Morimont, and Julien Hanson, and Vincent D'Orio, and Raymond Limet, and Philippe Kolh
Hemodynamic Research Center (HemoLiège), University of Liège, Liège 4000, Belgium. tsviny@hotmail.com

The aim of our study was to evaluate the effects of thromboxane A2 (TXA2) agonist, U-46619, on systemic circulatory parameters in the pigs before and after administration of a novel TXA2 receptor antagonist and synthase inhibitor (BM-573). Twelve anesthetized pigs were randomly assigned in two groups: in Ago group (n=6), the animals received six consecutive injections of U-46619 at 30 min interval, while in Anta group (n=6) they received an increasing dosage regimen of BM-573 10 min before each U-46619 injection. The effects of each dose of BM-573 on ex vivo platelet aggregation induced by arachidonic acid, collagen or ADP were also evaluated. Vascular properties such as characteristic impedance, peripheral resistance, compliance, arterial elastance were estimated using a windkessel model. Intravenous injections of 0.500 mg/ml of BM-573 and higher doses resulted in a complete inhibition of platelet aggregation induced by arachidonic acid. In the same conditions, BM-573 completely blocked the increase of arterial elastance, and stabilized both mean aortic blood pressure and mean systemic blood flow. In conclusion, BM-573 could therefore be a promising therapeutic approach in pathophysiological states where TXA2 plays a main role in the increase of vascular resistance like in pathologies such as systemic hypertension.

UI MeSH Term Description Entries
D010975 Platelet Aggregation Inhibitors Drugs or agents which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. Antiaggregants, Platelet,Antiplatelet Agent,Antiplatelet Agents,Antiplatelet Drug,Blood Platelet Aggregation Inhibitor,Blood Platelet Antagonist,Blood Platelet Antiaggregant,PAR-1 Antagonists,Platelet Aggregation Inhibitor,Platelet Antagonist,Platelet Antagonists,Platelet Antiaggregant,Platelet Antiaggregants,Platelet Inhibitor,Protease-Activated Receptor-1 Antagonists,Antiplatelet Drugs,Blood Platelet Aggregation Inhibitors,Blood Platelet Antagonists,Blood Platelet Antiaggregants,Platelet Inhibitors,Agent, Antiplatelet,Aggregation Inhibitor, Platelet,Antagonist, Blood Platelet,Antagonist, Platelet,Antiaggregant, Blood Platelet,Antiaggregant, Platelet,Drug, Antiplatelet,Inhibitor, Platelet,Inhibitor, Platelet Aggregation,PAR 1 Antagonists,Platelet Antagonist, Blood,Platelet Antiaggregant, Blood,Protease Activated Receptor 1 Antagonists
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013453 Sulfonylurea Compounds A class of compounds in which a sulfone functional group is attached to UREA. Compounds, Sulfonylurea
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D013928 Thromboxane A2 An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS). Rabbit Aorta Contracting Substance,A2, Thromboxane
D019796 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid A stable prostaglandin endoperoxide analog which serves as a thromboxane mimetic. Its actions include mimicking the hydro-osmotic effect of VASOPRESSIN and activation of TYPE C PHOSPHOLIPASES. (From J Pharmacol Exp Ther 1983;224(1): 108-117; Biochem J 1984;222(1):103-110) (15S)-Hydroxy-11 alpha, 9 alpha-(epoxymethano)prosta-5Z, 13E-dienoic Acid,(15S)hydroxy-9alpha,11alpha-(epoxymethano)prosta-5,13-dienoic acid,11 alpha,9 alpha-Epoxymethano PGH2,9,11-Dideoxy-11 alpha,9 alpha-epoxymethanoprostaglandin F2 alpha,9,11-Dideoxy-11 alpha,9-alpha-epoxymethano-PGF2 alpha,9,11-epoxymethano-PGH2,U-44619,U-46619,U44619,U46619,11 alpha,9 alpha Epoxymethano PGH2,9,11 epoxymethano PGH2,U 44619,U 46619
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

Related Publications

Vincent Tchana-Sato, and Jean-Michel Dogné, and Bernard Lambermont, and Alexandre Ghuysen, and David Magis, and Philippe Morimont, and Julien Hanson, and Vincent D'Orio, and Raymond Limet, and Philippe Kolh
January 1988, Pharmacology,
Vincent Tchana-Sato, and Jean-Michel Dogné, and Bernard Lambermont, and Alexandre Ghuysen, and David Magis, and Philippe Morimont, and Julien Hanson, and Vincent D'Orio, and Raymond Limet, and Philippe Kolh
January 1980, British journal of pharmacology,
Vincent Tchana-Sato, and Jean-Michel Dogné, and Bernard Lambermont, and Alexandre Ghuysen, and David Magis, and Philippe Morimont, and Julien Hanson, and Vincent D'Orio, and Raymond Limet, and Philippe Kolh
January 1984, Biomedica biochimica acta,
Vincent Tchana-Sato, and Jean-Michel Dogné, and Bernard Lambermont, and Alexandre Ghuysen, and David Magis, and Philippe Morimont, and Julien Hanson, and Vincent D'Orio, and Raymond Limet, and Philippe Kolh
January 1985, European journal of pharmacology,
Vincent Tchana-Sato, and Jean-Michel Dogné, and Bernard Lambermont, and Alexandre Ghuysen, and David Magis, and Philippe Morimont, and Julien Hanson, and Vincent D'Orio, and Raymond Limet, and Philippe Kolh
July 2003, The Journal of pharmacology and experimental therapeutics,
Vincent Tchana-Sato, and Jean-Michel Dogné, and Bernard Lambermont, and Alexandre Ghuysen, and David Magis, and Philippe Morimont, and Julien Hanson, and Vincent D'Orio, and Raymond Limet, and Philippe Kolh
July 1990, Chemical & pharmaceutical bulletin,
Vincent Tchana-Sato, and Jean-Michel Dogné, and Bernard Lambermont, and Alexandre Ghuysen, and David Magis, and Philippe Morimont, and Julien Hanson, and Vincent D'Orio, and Raymond Limet, and Philippe Kolh
September 1994, Journal of applied physiology (Bethesda, Md. : 1985),
Vincent Tchana-Sato, and Jean-Michel Dogné, and Bernard Lambermont, and Alexandre Ghuysen, and David Magis, and Philippe Morimont, and Julien Hanson, and Vincent D'Orio, and Raymond Limet, and Philippe Kolh
November 1993, European journal of pharmacology,
Vincent Tchana-Sato, and Jean-Michel Dogné, and Bernard Lambermont, and Alexandre Ghuysen, and David Magis, and Philippe Morimont, and Julien Hanson, and Vincent D'Orio, and Raymond Limet, and Philippe Kolh
September 1991, Lymphology,
Vincent Tchana-Sato, and Jean-Michel Dogné, and Bernard Lambermont, and Alexandre Ghuysen, and David Magis, and Philippe Morimont, and Julien Hanson, and Vincent D'Orio, and Raymond Limet, and Philippe Kolh
January 1987, Stroke,
Copied contents to your clipboard!